Nilsson et al. [Nilsson B M, Sundquist S, Johansson G, Nordvall G, Glas G, Nilvebrant L & Hacksell U; J. Med. Chem. 1995 38 473-487] describe the synthesis and muscarinic activity of certain 3-heteroaryl substituted quinuclidin-2-ene derivatives including 3-(2-benzofuranyl)quinuclidine-2-ene, 3-(3-benzofuranyl)quinuclidine-2-ene, 3-(2-benzothienyl)quinuclidine-2-ene, 3-(3-benzothienyl)quinuclidine-2-ene, 3-(2-benzoxazolyl)quinuclidine-2-ene, 3-(2-benzthiazolyl)quinuclidine-2-ene, 3-(2-benzofuranyl)quinuclidine and 3-(2,3-dihydrobenzofuran-2-yl)quinuclidine.
Nordvall et al. [Nordvall G, Sundquist S, Johansson G, Glas G, Nilvebrant L & Hacksell U; J. Med. Chem. 1996 39 3269-3277] describe the synthesis and muscarinic activity of certain quinuclidine-2-ene derivatives including 3-(2-benzofuranyl)-quinuclidine-2-ene and 3-(2-furo[3,2-b]pyridinyl)quinudidine-2-ene.
Johansson et al. [Johansson G, Sundquist S, Nordvall G, Nilsson B M, Brisander M, Nilvebrant L & Hacksell U; J. Med. Chem. 1997 40 3804-3819] describe the synthesis of certain quinuclidine-2-ene derivatives useful as muscarinic antagonists.
WO 93/23395 (Kabi Pharmacia) describes heteroaromatic quinuclidinenes and their activity on muscarinic acetylcholine receptors.
However, the 3-substituted heteroaromatic quinuclidine derivatives of the present invention have never been disclosed.